Ayyala-Somayajula Divya, Bottyan Thomas, Shaikh Suhail, Lee Brian P, Cho Stephanie H, Dodge Jennifer L, Terrault Norah A, Han Hyosun
Department of Internal Medicine, Division of Gastrointestinal & Liver Disease, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Department of Psychiatry, VA Northern California Health Care System, Sacramento, California, USA.
Liver Transpl. 2025 Apr 1;31(4):498-507. doi: 10.1097/LVT.0000000000000475. Epub 2024 Sep 3.
Acamprosate is a therapy for alcohol use disorder, but data on feasibility and safety in recipients of liver transplants are lacking. This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18 y) with liver transplant for alcohol-associated liver disease enrolled between 2021 and 2023, who were randomized 2:1 to the intervention of acamprosate (666 mg dose 3 times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety (prevalence of adverse events [AEs]), feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use >60%), and efficacy (reduction in Penn Alcohol Craving Scale), and relapse-blood phosphatidylethanol (≥20 ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention-to-treat (excluding withdrawals before medication administration) and per-protocol population (excluding withdrawals/<4 weeks participation). Of 78 participants who were approached, 30 enrolled (19 acamprosate and 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate before medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p > 0.99), including grade 3 AEs (53.9% vs. 60.0%, p > 0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate versus SOC groups (61.0% vs. 76.0%, p = 0.19), and 69.0% were acamprosate adherents. Baseline Penn Alcohol Craving Scale values were low with no difference by the group in median absolute change in Penn Alcohol Craving Scale for intention-to-treat (0, IQR: -4 to 0 vs. 0, IQR: 0-0, p = 0.32), and per-protocol analyses (-1, IQR: -6 to 0 vs. 0, IQR: -0 to 0, p = 0.36). There was no reported or biochemical evidence of alcohol relapse. In this pilot study, preliminary data suggest that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-liver transplant care (ClinicalTrials.gov, Number: NCT06471686).
阿坎酸是一种治疗酒精使用障碍的药物，但缺乏关于肝移植受者使用该药物的可行性和安全性的数据。这是一项单中心、非盲、前瞻性试点随机对照试验，研究对象为2021年至2023年期间因酒精性肝病接受肝移植的成年人（≥18岁），他们被按2:1随机分配至阿坎酸干预组（剂量为666毫克，每日3次）或标准治疗组（SOC），为期14周。观察指标包括安全性（不良事件发生率）、可行性（每周调查回复率>60%）、依从性（自我报告的阿坎酸使用率>60%）、疗效（宾夕法尼亚酒精渴望量表评分降低）以及通过标准化每周调查评估的复发性血液磷脂酰乙醇（≥20纳克/毫升/报告饮酒情况）。疗效分析在意向性分析人群（排除用药前退出者）和符合方案人群（排除退出者/<4周参与者）中进行。在78名被邀请的参与者中，30人入组（19名阿坎酸组和11名SOC组），两组基线特征相似。八名参与者退出（6名阿坎酸组在用药前退出，2名SOC组）。阿坎酸组和SOC组的不良事件相似（92.3%对90.0%，p>0.99），包括3级不良事件（53.9%对60.0%，p>0.99），未报告4/5级不良事件。阿坎酸组和SOC组的调查回复率相似（61.0%对76.0%，p = 0.19），69.0%的阿坎酸组参与者依从。意向性分析中，两组的基线宾夕法尼亚酒精渴望量表值较低，宾夕法尼亚酒精渴望量表的中位数绝对变化在两组间无差异（0，四分位间距：-4至0对0，四分位间距：0-0，p = 0.32），符合方案分析中也是如此（-1，四分位间距：-6至0对0，四分位间距：-0至0，p = 0.36）。未报告酒精复发的情况或有生化证据表明酒精复发。在这项试点研究中，初步数据表明阿坎酸可能是安全可行的。这些数据可为更大规模的研究以及临床医生在肝移植后护理中解决酒精使用障碍的努力提供参考（ClinicalTrials.gov编号：NCT06471686）。
